Abstract 9341: Increased Expression of ATPase (Beta) During Late Preconditioning and Preserved Energetics During Low Flow Ischemia in Swine
Background: Complex V protein, an ATPase within the electron transport chain (ETC) of mitochondria, is increased in preconditioned hearts and may play an important role in maintaining tissue ATP during myocardial ischemia. Using a proteomic approach with iTRAQ, we determined the expression of ETC proteins including ATPase in the Second Window of Protection (SWOP) and tested whether the energetic state was more favorable in SWOP versus SHAM pigs during subsequent regional myocardial ischemia.
Methods: Fourteen pigs underwent a SWOP protocol with ten 2-min. balloon inflations in the LAD, each separated by 2 min. reperfusion. Twenty-four hours later, mitochondria were isolated from SWOP (N=7) and SHAM (N=6) hearts and proteomic changes were determined by iTRAQ. Using a Clark electrode, oxygen respiration was measured during State 3 and State 4 conditions and the respiratory control index (RCI) was calculated (State 3/State4) prior to and following 10 min anoxia. In parallel in vivo studies, high-energy nucleotides were obtained by transmural biopsy from anesthetized SWOP and SHAM pigs at baseline and during a 25%; sustained LAD blood flow reduction.
Results: In isolated mitochondria, the RCI from SWOP was similar to SHAM at baseline (4.1±0.3 vs 3.7±0.3; P=0.30) but greater post-anoxia (1.9±0.4 vs 1.1±0.2; P<0.05). Using iTRAQ, ATPase (Beta) expression was >40%; higher while during in vivo studies, the transmural energetic state, as estimated by the free energy of ATP hydrolysis was more favorable during low-flow ischemia in SWOP versus SHAM hearts (Figure).
Conclusions: ATPase expression is increased in mitochondria from SWOP heart tissue and may account for the favorable energetic state during low flow ischemia and in ex vivo mitochondria. These data support the notion that increased expression of Complex V proteins within the ETC of mitochondria impart a favorable energetic effect during sustained oxygen deprivation.
- Mitochondrial energetics, heart failure, arrhythmias
- Cardiac metabolism
- Ischemic heart disease
- © 2010 by American Heart Association, Inc.